Role of Cathepsin S in Periodontal Inflammation and Infection

1Section of Experimental Dento-Maxillo-Facial Medicine, Center of Dento-Maxillo-Facial Medicine, University of Bonn, Bonn, Germany2Department of Orthodontics, Center of Dento-Maxillo-Facial Medicine, University of Bonn, Bonn, Germany3Department of Diagnosis and Surgery, School of Dentistry at Araraquara, Sao Paulo State University (UNESP), Araraquara, SP, Brazil4Department of Periodontology, Laboratory for Oral Microbiology, School of Dental Medicine, University of Bern, Bern, Switzerland5Discipline of Orthodontics, Faculty of Dentistry, University of Sydney, Sydney, NSW, Australia6Institute of Reconstructive Neurobiology, Life & Brain Center, University of Bonn, Bonn, Germany7Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, Bonn, Germany8Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece9Noel Martin Visiting Chair, Faculty of Dentistry, University of Sydney, Sydney, NSW, Australia

Abstract

Cathepsin S is a cysteine protease and regulator of autophagy with possible involvement in periodontitis. The objective of this study was to investigate whether cathepsin S is involved in the pathogenesis of periodontal diseases. Human periodontal fibroblasts were cultured under inflammatory and infectious conditions elicited by interleukin-1β and Fusobacterium nucleatum, respectively. An array-based approach was used to analyze differential expression of autophagy-associated genes. Cathepsin S was upregulated most strongly and thus further studied in vitro at gene and protein levels. In vivo, gingival tissue biopsies from rats with ligature-induced periodontitis and from periodontitis patients were also analyzed at transcriptional and protein levels. Multiple gene expression changes due to interleukin-1β and F. nucleatum were observed in vitro. Both stimulants caused a significant cathepsin S upregulation. A significantly elevated cathepsin S expression in gingival biopsies from rats with experimental periodontitis was found in vivo, as compared to that from control. Gingival biopsies from periodontitis patients showed a significantly higher cathepsin S expression than those from healthy gingiva. Our findings provide original evidence that cathepsin S is increased in periodontal cells and tissues under inflammatory and infectious conditions, suggesting a critical role of this autophagy-associated molecule in the pathogenesis of periodontitis.